关于成人碘安全摄入量的探讨

目的探讨成人碘的安全摄入量。方法选择甲状腺功能正常的(22.54±2.65岁)健康志愿者。随机分为7组,各组每人每日分别服用500,750,1000,1250,1500,1750,2000μg的碘剂,为期4w。于实验前、实验第2w以及实验结束时分别采集志愿者空腹血、晨尿。用化学发光免疫分析法测定血清FT4、灵敏促甲状腺激素(sTSH),定量放免法测定甲状腺过氧化物酶抗体(thyroid peroxidase antibody,TPOAb)、甲状腺球蛋白抗体(thyroglobulin antibody,TGAb)浓度,用砷铈氧化还原法测定尿碘水平。对被调查者进行为期7 d的膳食调查。采集天津市市售食物、饮用水样品,以及食盐样品,测定其碘含量。结果补碘前人群碘摄入水平充足,尿碘中位数为272.25μg/L,被调查者膳食碘摄入的平均值(含碘盐)为346.24μg/d。与补充碘剂前相比,补碘后各组人群尿碘水平明显增加;血清FT4在正常值范围内下降;各组人群在补充碘剂2 w后血清sTSH明显上升,与补碘前相比增加近1倍多,至4 w后增加近2倍。各剂量组间相比血清sTSH变化幅度基本一致。正常人群补充500～2000μg碘剂2 w后出现了亚临床甲状腺功能减退,各剂量组的发病率在15.00%~47.37%之间。试验结束时未见临床甲减患者。结论正常人群补充500μg/d碘即可引起亚临床甲状腺功能减退。因此,对于生活在碘营养充足地区的人群每日碘的补充剂量不宜超过500μg,结合每日膳食碘的摄入量,我们建议碘的可耐受的最高摄入量(UL)的上限值应低于900μg。     

Sporotrichosis in north-east India

Reports on the occurrence of sporotrichosis in some parts of north-east India are scarce. We report here five cases of lymphocutaneous sporotrichosis from north-east India, including one from Sikkim State and four from distant places in the north-eastern part of West Bengal. All patients were full or part-time farmers or gardeners. Diagnosis of sporotrichosis was confirmed by isolation of Sporothrix schenckii in culture and in vitro conversion of the isolates to yeast form. The cases were treated with 50% solution of potassium iodide.     

Rottlerin inhibits human T cell responses

Rottlerin is a pharmacological inhibitor of protein kinase C (PKC) theta, a novel PKC selectively expressed in T lymphocytes. PKC theta is known to regulate T cell receptor (TCR)/CD28 signalling pathways in T lymphocytes, but the impact of PKC theta inhibition on human T cell responses remains undefined. In this work, we describe the effects of rottlerin on the responses of CD4+ and CD8+ human T lymphocytes upon polyclonal activation. We observed a dose-dependent inhibition of CD4+ and CD8+ T cell proliferation in response to anti-CD3/anti-CD28 antibodies stimulation in the presence of rottlerin. This inhibition was associated with impaired CD25 expression and decreased interleukin (IL)-2 production in activated T cells. In contrast, rottlerin did not alter IL-2-induced T cell proliferation. Furthermore, we demonstrated that rottlerin blocked interferon (IFN) gamma, IL-10 and IL-13 mRNA expression in TCR/CD28 activated CD4+ T cells. These findings place rottlerin as a potent immunosuppressive agent for the development of novel therapies in T cell mediated immune disorders.     

Differential Toxicity of Parenteral Antibiotic Drugs in Renal Cells (LLC-PK1) Grown on Permeable Membrane Filters

Growth of renal epithelial cells on permeable membrane niters promotes the expression of polarized function and facilitates the study of directional aspects of exposure of kidney cells to nephrotoxins (apical versus basolateral). Monolayer cultures of LLC-PK₁ cells were grown on membrane filter inserts coated with a collagen-laminin matrix and incubated with three parenteral antibiotic drugs (vancomycin, 2.5–15 mg/ml; tobramycin, 0.5–10 mg/ml; and cephaloridine, 0.05–0.5 mg/ml) at 37d`C for 48 h. Growth medium containing the experimental antibiotic drugs was placed in the upper or lower chamber for apical or basolateral exposure, respectively. After incubation, cellular viability was determined by nigrosin dye exclusion and by the in situ uptake of the fluorescent dye, propidium iodide, which is increased in dead cells. Cytotoxicity was seen with increasing concentrations of each antibiotic drug after basolateral or apical exposure. Profound basolateral and apical differences, expressed as a percent of control viability, were observed with all three antibiotic drugs when viability was assessed by nigrosin dye exclusion. Basolateral versus apical percent viabilities were 0 versus 67% with vancomycin (15 mg/ml), 38 versus 76% with tobramycin (5 mg/ml), and 4 versus 89% with cephaloridine (0.2 mg/ml). No significant differences in toxicity were observed after basolateral and apical exposure to vancomycin and tobramycin when propidium iodide was used as the viability endpoint. Cytotoxicity due to cephaloridine, on the other hand, was greater after basolateral exposure by propidium iodide monitoring (e.g., 4,046 versus 2,628 relative fluorescence units after basolateral versus apical exposure, respectively, at 0.25 mg/ml). These results demonstrate enhanced sensitivity of LLC-PK₁ cells to nephrotoxins from the basolateral surface and also identify differences between cellular viability end-points.     

Protective effect of N-acetylcysteine against BDE-209-induced neurotoxicity in primary cultured neonatal rat hippocampal neurons in vitro

Globally, brominated diphenyl ether-209 (BDE-209) is the most widely used polybrominated diphenyl ether (PBDEs). It has been reported that BDE-209 induces developmental neurotoxicity in vivo. The purpose of this study was to use an antioxidant, N-acetylcysteine (NAC), as an antidote for the neurotoxic effect of BDE-209. We used primary hippocampal neurons from rats for the in vitro cultures. BDE-209 was added to the cultures in increasing concentrations and co-cultured with NAC in order to assess the effect of NAC on BDE-209-induced neurotoxicity. We measured cell viability, apoptosis, expression of phosphorylated p38 mitogen-activated protein kinases (MAPK), intracellular calcium content, and intracellular reactive oxygen species (ROS) levels. The difference between the BDE-209 groups without NAC and the blank control groups was significant (P < 0.05). The difference between the NAC treatment groups and the BDE-209 groups without NAC was also significant (P < 0.05), showing that BDE-209 increased apoptosis, the expression of p38 MAPK, the calcium ion concentration, and the ROS level and decreased cell viability. In contrast, NAC reduced the degree of cellular cytotoxicity induced by BDE-209. The results suggested that NAC may be able to attenuate BDE-209-induced neurotoxicity.     

Esculetin modulates cytotoxicity induced by oxidants in NB4 human leukemia cells

Esculetin is a polyphenolic compound with cytoprotective properties. We previously demonstrated the induction of apoptosis by esculetin in NB4 human leukemia cells, as a model, by a mechanism not well understood. To analyse the antioxidant activity of esculetin on apoptosis, we have studied the influence of co-treatments of esculetin at a concentration of 100 μM with exogenous ROS donors, namely tert-butyl-hydroperoxide and hydrogen peroxide, on NB4 cells. Esculetin (100 μM) exerts a protective effect on cell viability and death necrosis or late apoptosis caused by the oxidant t-BHP whereas it potentiates decrease of cell viability and cell death caused by H₂O₂. In the first case, the O₂^? scavenging activity of esculetin (100 μM) could be implicated. In the last one, cytotoxicity by apoptosis induction seems to be related to the increase in O₂^?, among other possible mechanisms. These results contribute to the study of the antitumor properties of esculetin by regulation of redox balance in leukemia cells.     

Induction of cell death and modulation of Annexin A1 by phytoestrogens in human leukemic cell lines

BackgroundPhytoestrogens are polyphenolic plant compounds which are structurally similar to the endogenous mammalian estrogen, 17β-estradiol. Annexin A1 (ANXA1) is an endogenous protein which inhibits cyclo-oxygenase 2 (COX-2) and phospholipase A2, signal transduction, DNA replication, cell transformation, and mediation of apoptosis.ObjectiveThis study aimed to determine the effects of selected phytoestrogens on annexin A1 (ANXA1) expression, mode of cell death and cell cycle arrest in different human leukemic cell lines.MethodsCells viability were examined by MTT assay and ANXA1 quantification via Enzyme-linked Immunosorbent Assay. Cell cycle and apoptosis were examined by flow cytometer and phagocytosis effect was evaluated using haematoxylin-eosin staining.ResultsCoumestrol significantly (p < 0.05) reduced the total level of ANXA1 in both K562 and U937 cells and genistein significantly (p < 0.05) reduced it in K562, Jurkat and U937 cells, meanwhile estradiol and daidzein induced similar reduction in U937 and Jurkat cells. Coumestrol and daidzein induced apoptosis in K562 and Jurkat cells, while genistein and estradiol induced apoptosis in all tested cells. Coumestrol and estradiol induced cell cycle arrest at G2/M phase in K562 and Jurkat cells with an addition of U937 cells for estradiol. Genistein induced cell cycle arrest at S phase for both K562 and Jurkat cells. However, daidzein induced cell cycle arrest at G0/G1 phase in K562, and G2/M phase of Jurkat cells. Coumestrol, genistein and estradiol induced phagocytosis in all tested cells but daidzein induced significant (p < 0.05) phagocytosis in K562 and Jurkat cells only.ConclusionThe selected phytoestrogens induced cell cycle arrest, apoptosis and phagocytosis and at the same time they reduced ANXA1 level in the tested cells. The IC50 value of phytoestrogens was undetectable at the concentrations tested, their ability to induce leukemic cells death may be related with their ability to reduce the levels of ANXA1. These findings can be used as a new approach in cancer treatment particularly in leukemia.     

Pregnancy-associated glycoprotein (PAG) family localized in chorionic cells within the epitheliochorial/diffuse placenta of the alpaca (Lama pacos)

Pregnancy-associated glycoproteins (PAGs) are abundant embryo-originated products expressed in the pre-placental trophoblast and later in the post-implantational chorionic epithelium of some ungulate species. This paper describes the cellular immunolocalization of the chorionic PAG family in the epitheliochorial placenta type of the alpaca (Lama pacos—Lp), in which the PAGs were named ‘LpPAGs’. Placental Lp sections (5 μm) of different females near mid-pregnancy (150 days post coitum; dpc), advanced pregnancy (244-263 dpc) and late pregnancy (347 dpc) were used for cross-species (heterologous—ht) double fluorescent immunohistochemistry (htdF-IHC). The htdF-IHC was performed with primary rabbit polyvalent anti-porcine PAG polyclonals. The LpPAG immuno-complexes were visualized with secondary goat anti-rabbit immunoglobulins-conjugated with Alexa 488 fluorophore (green), among all nuclei of placental cells stained with propidium iodide (red). This is the first study reporting the immunolocalization of the LpPAG family identified by htdF-IHC at the feto/maternal interface during different pregnancy stages of the alpaca. The most dominant and strongest immune-positive LpPAG signals were found in the well-developed chorionic cell layer. Our htdF-IHC indicated relatively high epitope resemblance to that of the PAGs in camelids and pigs. These data increase our general knowledge of chorionic PAG localization during pregnancy-stage dependent development of the epitheliochorial diffuse placenta type in the alpaca.     

碘化钾碘酸钾对缺碘大鼠脑组织抗氧化能力的实验研究

目的：研究碘化钾、碘酸钾对大鼠脑组织抗氧化能力的影响。方法：将低碘wistar大鼠30只随机分为3组。低碘组（LI），碘化钾组（KI），碘酸钾组（KIO3）。3个月后分别测定30只大鼠脑组织中超氧化物歧化酶（SOD），谷光甘肽过氧化物酶（GPx)及脂质过氧化产物丙二醛（MDA）。结果：碘化钾及碘酸钾组脑组织GPx含量高于低碘组。结论：对于低碘大鼠经过3个月的补碘治疗，无论是碘化钾还是碘酸钾都具有良好的治疗效果，两种不同碘制剂对于脑组织抗氧化能力的影响无显著性差异。